Atopic Comorbidities Research Articles

Dupilumab is efficacious in patients with prurigo nodularis regardless of history of atopic comorbidities: Pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Dupilumab is efficacious in patients with prurigo nodularis regardless of history of atopic comorbidities: Pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Atopic dermatitis in children: a cross-sectional study of its impact on quality of life

Background: Atopic dermatitis, characterized by chronic inflammation of the skin, manifests with symptoms such as itching, skin discomfort, and sleep disturbances, significantly impacting the physical health and daily functioning of affected children. We embarked on this study to assess the Quality of Life of children with AD, identify factors that influence their QoL, and determine the specific domains of QoL most affected by the condition. Methods: Children up to 16 years of age, who met the Hanifin and Rajka’s diagnostic criteria for AD, were identified. The severity of AD was assessed using the severity scoring of atopic dermatitis index, and QoL was assessed using validated questionnaires: the infants dermatitis quality of life index for children under 4 years and the children’s dermatology life quality index for children 4 years and above. Results: A total of 70 children with AD were enrolled in the study. The mean QoL (IDQOL/CDLQI) score for children with AD was 6.7±5.05 and QoL was significantly impaired in children with more severe disease. The domains of QoL most affected by AD were related to pruritus, sleep disturbances, mood changes and treatment related issues. The duration of illness and the presence of other atopic comorbidities showed a significant correlation with QoL impairment, whereas age, gender and socioeconomic status demonstrated no such correlation. Conclusions: This study highlights the substantial impact of AD on the QoL of affected children, especially due to symptoms like itching and sleep disturbances.

Characteristics and Management of Patients with Alopecia Areata and Selected Comorbid Conditions: Results from a Survey in Five European Countries.

Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss and can impose a high psychosocial burden on patients. The presence of comorbid conditions may impact the management of AA in clinical practice. This analysis aims to describe disease characteristics and management of AA in patients with concomitant atopic, autoimmune, and psychiatric comorbid conditions. Data were collected from the Adelphi Disease Specific Programme™, a cross-sectional survey of physicians and their adult patients with AA conducted in France, Germany, Italy, Spain, and the UK between October 2021 and June 2022. Patients' disease severity was based on physician's definition. Physician-reported data on demographics, AA clinical characteristics, comorbid conditions, and information related to AA therapies were analyzed. Analyses were descriptive. Overall, 239 dermatologists provided data for 2083 patients, of which 558 patients (27%) had at least one atopic, autoimmune, or psychiatric comorbid conditions. The most common comorbid conditions were atopic dermatitis, autoimmune thyroid disease, and anxiety. The mean (standard deviation) patient age for the three comorbidity groups was 37.6years (12.1) and 56% of the patients were women (n = 313). In the three comorbidity groups, 51%, 50%, and 55% of patients with atopic, autoimmune, and psychiatric comorbidities had severe AA with disease progression reported as worsening in 30%, 28%, and 30%, respectively, whereas in the group with no comorbidities, 37% were described as having severe AA and 21% getting worse. Scalp hair loss was the primary sign reported across the three groups of comorbid conditions (atopic, 91%; autoimmune, 91%; psychiatric, 88%). Patients with preselected comorbidities presented more frequently AA-related signs and symptoms beyond scalp hair loss than patients without comorbid conditions. These patients were also more likely to receive topical calcineurin inhibitors, topical immunotherapy, conventional systemic immunosuppressants, and oral Janus kinase inhibitors for the treatment of their AA. This analysis provided insights into the burden and management of AA in patients presenting with atopic, autoimmune, and psychiatric comorbid conditions in five European countries.

Associations of demographics, aggravating factors, comorbidities, and treatments with atopic dermatitis severity in China: A national cross-sectional study.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China. This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors. Overall, 16,838 respondents were included in the final analysis (age 30.9±24.1years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions. To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy. ClinicalTrials.gov Identifier: NCT05316805, CORNERSTONE.

Severe atopic dermatitis in early infancy: characteristics, challenges and new perspectives in clinical practice.

Atopic dermatitis (AD) is the most common skin disease in infants and children with a prevalence of 10% in the first two years of life. In this age group up to 15% are severely affected. "Children are not little adults" - this applies in particular to infants with severe atopic dermatitis. Age-specific clinical aspects (psychosocial, neurocognitive, morphological) of the disease require an adjusted disease management. Considering recent approval of systemic treatment options, early identification of infants and children with severe and early persistent disease is of particular importance also in view of possible prevention of atopic comorbidity. As several inborn errors of immunity (IEI) share features of the atopic phenotype, it is essential for clinicians to distinguish signs of immunodeficiency from severe AD. Here, we describe a practical approach on the basis of clinical history and key dermatological and laboratory findings. Furthermore, this paper is aimed at providing an update on general management of severe AD in early infancy, including recommendations for systemic treatment.

A survey on prevalence and parents’ perceptions of food allergy in 3- to 16-year-old children in Wuhan, China

BackgroundThe prevalence of food allergy (FA) has risen in recent decades, yet there is limited data on the cognition and beliefs of FA among the parents of FA children. ObjectiveTo investigate the prevalence of FA and assess the knowledge and perception of FA among parents of FA children in Wuhan, China. MethodsOnline questionnaires were conducted for the parents of 3- to 16-year-old children. They reported symptoms of suspected FA in the screening questionnaire were interviewed for further diagnostic evaluation. All the parents of the suspected FA children completed the subsequent assessments of the knowledge and perception on FA as well as their attitude towards the current online platforms. ResultsA total of 1963 children were recruited. The prevalence of self-reported FA was 10.2% (95% CI: 8.1–12.4%) and the physician-diagnosed FA was 6.2% (95% CI: 5.1–7.2%) in 3- to 16-year-olds in Wuhan. And the children with family history (57.9%) were predisposed to developing FA (P＜0.001). The total Brief Illness Perception Questionnaire (B-IPQ) score was 41.3 ± 10.0 among the parents. The B-IPQ scores correlated with symptom onset, but not with family history or other atopic comorbidities. The parents who never sought treatments obtained lower B-IPQ scores on most items compared to those who received treatments. The accuracy rate of the FA knowledge questionnaire was 56.7%. 11.6% of participants reported that children's FA had an impact on their lives. 67.2% of participants had searched information of FA online, among whom 80% expected to obtain professional suggestions on management and prevention strategies of FA from online platform. ConclusionIn 3- to 16-year-old children in Wuhan, the prevalence of self-reported and physician-diagnosed FA was 10.2% and 6.2% respectively. Parents’ knowledge of FA was insufficient and only a small proportion of parents perceived that their lives and careers have been affected considerably by FA of their children. Patient education and current online platforms should be improved among parents of FA children.

548 - Tralokinumab improves signs and symptoms of moderate-to-severe atopic dermatitis in patients aged 12 years and older with and without atopic comorbidities

Abstract Introduction/Background Atopic dermatitis (AD) is an inflammatory skin disease associated with atopic comorbidities, including asthma, food allergy, hay fever, and allergic conjunctivitis. Tralokinumab, a high-affinity monoclonal antibody that specifically targets IL-13, is indicated for the treatment of moderate-to-­severe AD. Objectives To assess the impact of atopic comorbidities on the efficacy and safety of tralokinumab vs. placebo for moderate-to-­severe AD in patients age ≥12 years. Methods This post-hoc analysis presents data from the adult trials ECZTRA 1 and 2 (NCT03131648 and NCT03160885 pooled; 300 mg tralokinumab every 2 weeks [Q2W] vs. placebo) and ECZTRA 3 (NCT03363854; 300 mg tralokinumab Q2W vs. placebo, both plus TCS as needed), and the ECZTRA 6 adolescent trial (NCT03526861; pooled 150 mg and 300 mg tralokinumab Q2W vs. placebo). Tralokinumab-treated patients received a loading dose. Proportion of patients achieving IGA 0/1 and EASI-75 at Week 16 according to patient-reported current or past atopic comorbidity are presented as observed regardless of rescue medication use; missing data were imputed as non-responders. Results In total 2,223 patients were included across four trials. Among patients in ECZTRA 1 and 2, 50.5% reported history of asthma, 38.5% food allergy, 53.8% hay fever, and 33.5% allergic conjunctivitis, while 19.8% reported no atopic comorbidities and 79.3% reported ≥1 atopic comorbidity. Proportions of patients in ECZTRA 3 and 6 reporting history of atopic comorbidities were largely similar, although more adolescent patients reported food allergy. In all subgroups at Week 16, higher proportions of patients receiving tralokinumab vs. placebo achieved EASI-75. In ECZTRA 1 and 2, response rates among patients in each subgroup were asthma: 35.3% vs. 12.8%, food allergy: 33.2% vs. 14.7%, hay fever: 36.8% vs. 16.5%, allergic conjunctivitis: 34.8% vs. 12.7%, none: 34.6% vs. 20.5%; and ≥1 atopic comorbidity: 35.5% vs. 15.2% (P<0.05 for all). A similar pattern of response was observed in ECZTRA 3 and 6, and for IGA 0/1 across trials. EASI-75 response rates for tralokinumab-treated patients were consistent across patients with different numbers of atopic comorbidities. Safety across subgroups was consistent with the safety profile of tralokinumab observed overall in adults and adolescents. Conclusions 16 weeks of tralokinumab treatment improved AD signs and symptoms in adult and adolescent patients with and without atopic comorbidities, regardless of type or number of atopic comorbidities. The safety profile of tralokinumab was consistent between patients with and without atopic comorbidities.

506 - Dupilumab is efficacious in patients with prurigo nodularis regardless of history of atopic comorbidities: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules. Nearly half of affected adult patients have a history of (or current) atopic comorbidity, such as atopic dermatitis (AD). Objective To report the efficacy and safety of dupilumab in patients with PN with or without history of atopic comorbidities, in a pre-specified analysis of pooled data from two phase 3 trials. Method In the randomized, double-blind, placebo-controlled, 24-week studies, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), adults with PN inadequately controlled by topical prescription therapies, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. Atopic patients were defined as patients with a physician-documented history, or current diagnosis, of at least one of the following atopic comorbidities: AD, allergic rhinitis/rhinoconjunctivitis, asthma, or food allergy. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; 0–10), and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; 0–4). Results 311 patients were randomized (dupilumab n=153, atopic/non-atopic N=67/86; placebo n=158, atopic/non-atopic N=68/90). At Week 24, significantly more atopic and non-atopic dupilumab-treated patients achieved a ≥4-point improvement in WI-NRS (58.2%/59.3%), and an IGA PN-S score of 0 or 1 (52.2%/41.9%) vs placebo (20.6%/17.8% [nominal P<0.0001/P<0.0001] and 16.2%/17.8% [nominal P<0.0001/P=0.0005], respectively). The proportion of patients achieving concomitant ≥4-point improvement in WI-NRS and IGA PN-S score of 0 or 1 was higher for both dupilumab-treated atopic and non-atopic patients (37.3%/33.7%) vs placebo (7.4%/10.0% [nominal P=0.0057/P<0.007]). Overall safety was consistent with the known dupilumab safety profile, with no remarkable differences between atopic and non-atopic patients. Conclusion Dupilumab treatment improves itch and skin lesions in PN patients with and without a history of atopic comorbidities, indicating that underlying type 2 inflammation is present in patients with PN regardless of their history of atopic comorbidities.

557 - Tralokinumab real-world use in adults with atopic dermatitis: baseline characteristics of the first 100 patients recruited to the TRACE study in the United States

Abstract Introduction/Background Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols. Objectives TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice. Methods TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients. Results Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation [SD]) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator’s Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness. Conclusions Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life.

487 - Adult atopic dermatitis is associated with impaired oral health and oral dysbiosis - a case-control study

Abstract Background Previous studies linked chronic oral diseases to skin disorders such as psoriasis. However, data about oral health and oral microbiota in atopic dermatitis (AD) is sparse. Objectives To compare the oral health status and oral microbiota of AD patients and healthy controls. Methods This was a prospective sex and age- matched case-control study comparing adult participants with and without dermatologist-verified AD. Exclusion criteria included recent use of oral, topical, or systemic medication that could affect oral health or microbiome assessment. Oral health indices including Gingival Index, Plaque Index, Oral Hygiene Index, Caries Severity Index and prosthodontics status, were assessed by a dentist. Samples of oral flora were collected and subjected to high-throughput 16S rRNA gene sequencing analysis for microbiome analysis. Results Forty-five AD participants and 41 non-AD controls were recruited. The two groups had no significant differences in terms of their demographic and clinical characteristics, except for the higher rate of atopic co-morbidities in the AD group (p<.001). Compared to the control group, participants with AD had significantly poorer plaque (p=0.04) and oral hygiene indices (p=0.04) and a trend towards higher gingival index (p=0.05). The results of the Faith phylogenetic diversity (FDR) test indicated that the oral microbial diversity in the AD group was significantly higher (α-diversity, FDR-adjusted p=0.0007) when compared with the control group. Characterization of the similarities and differences in the composition of the microbial communities between the samples (β-diversity) from the AD patients and controls indicated that they clustered separately. The groups showed significant dissimilarity and distinct clustering of microbial abundance (FDR-adjusted p=0.001). Importantly, higher community diversity was previously linked to periodontitis and gingival disease. Furthermore, AD patients had a significantly increased abundance of taxa correlated with oral diseases and decreased abundance of oral health-associated bacteria. Conclusion AD appears to be associated with poorer oral health and oral dysbiosis, and thus, there is a need to increase the awareness of both patients and physicians about oral health.

Molecular profiling in bee venom allergy: clinical and therapeutic characterization in a Portuguese cohort.

Background. Bee venom allergy (BVA) can trigger local and systemic allergic reactions, including anaphylaxis. Recently, the molecular sensitization profile has gained importance in the reaction's stratification and venom immunotherapy (VIT). Methods. Retrospective analysis of patients with hypersensitivity to BVA, confirmed by specific sIgE to Apis mellifera ≥0.35 kU/L and/or positive skin tests to bee venom commercial extract, evaluated in specialized consultation. Demographic, clinical, and laboratory data (including molecular Api m 1, 4, and 10) were analyzed, looking for risk factors associated with the severity of the index reaction and reactions during VIT. Results. 93 patients were included (55.9% male; median age of 46 years), 57.3% with atopic comorbidities, and 23.4% with cardiovascular comorbidities. The median specific IgE to Apis mellifera was 6.7 kU/L (IQR 1.0-20.3) kU/L. Regarding the molecular profile, the median IgE to Api m 1 was 0.5 kU/L (57.5% positive out of all measurements); Api m 4 - 0.01 kU/L (11.9% positive), and Api m 10 - 0.3 kU/L (50.0% positive). No patient was monosensitized to Api m 4. The median age of the most severe sting reaction was 36 (IQR 26-48) years, with a median severity (Müeller scale) of 3 (IQR 2-3). Forty-seven patients (50.5%) underwent VIT, with 35.6% of reactions recorded. Allergic reactions during VIT were recorded in 35.6% of cases. The severity of the index reaction correlated positively with older ages (p=0.040; r=0.249), in contrast to monosensitization to Api m 1, which was an independent predictor of milder reactions (p=0.015). Sensitization to Api m 10 was associated with a higher likelihood of reactions during VIT (p=0.038) but potentially less systemic reactions at re-stings (p=0.097). Conclusions. Molecular sensitization profile appears to be relevant not only to the severity of index reactions but also during VIT. Studies of a large cohort of patients with molecular profiles are essential to validate these results and improve the clinical and therapeutic approach to BVA.

Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis.

Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients. Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by "limma" were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein-protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated. The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees. The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.

Insights Into Pediatric Asthma: A Population Study From Alto Minho Health Center.

Background Asthma represents one of the most common diseases in childhood, with a prevalence ranging between 9% and 13% in Portugal. Therefore, it holds significant importance in pediatric health. While existing studies have shed light on asthma in the Portuguese population, they have predominantly concentrated on urban centers, with the population of Alto Minho remaining underrepresented in the literature. This study aims to understand the main factors of exposure, exacerbation, and the most prevalent allergens in a pediatric sample from the Alto Minho Local Health Unit, Portugal. Methodology A retrospective cohort study was conducted among 239 pediatric asthma patients aged between five and 18 years at the Alto Minho Health Center.Data on demographics, clinical information, family history, environmental exposures, exacerbating factors, and prick test results were analyzed. Results Of the 239 patients, 64.44% were male and 35.56% were female. The majority of the sample exhibited a normal body mass index (82.17%) and a family history of atopy (66.67%). Noteworthy patterns emerged in comorbidities, notably an increased association with allergic rhinitis, the most frequent concomitant atopic pathology (79.50%), followed by atopic dermatitis (27.61%) and food allergy (10.88%). Sensitization to dust mites, particularly Dermatophagoides pteronyssinus, was widespread among the participants. Environmental exposures were marked by significant factors such as proximity to plants and trees, soft toys, and living in rural areas. Exacerbating factors included common triggers such as exercise, seasonal variations, and even laughter. Statistically significant associations were found between atopic comorbidities, exacerbation factors, exposure factors, and prick test results. Conclusions Our findings align with global trends, emphasizing the prevalence of atopic pathologies in pediatric asthma. Sensitization patterns and environmental exposures are indicative of regional influences. Study limitations include sample size and data standardization issues. Despite these limitations, the study significantly contributes to understanding pediatric asthma in Alto Minho, offering valuable insights for prompt diagnosis and targeted treatments.

Tralokinumab Improves Signs and Symptoms of Moderate-to-Severe Atopic Dermatitis in Patients Aged 12 years and Older With and Without Atopic Comorbidities

Background: Atopic dermatitis (AD) is an inflammatory skin disease associated with atopic comorbidities, including asthma, food allergy, hay fever, and allergic conjunctivitis. Tralokinumab, a high-affinity monoclonal antibody that specifically targets IL-13, is indicated for the treatment of moderate-to-severe AD. We assessed the impact of atopic comorbidities on the efficacy and safety of tralokinumab vs. placebo for moderate-to-severe AD in patients age ≥12 years.
 Methods: This post-hoc analysis presents data from the adult trials ECZTRA 1 and 2 (NCT03131648 and NCT03160885 pooled; 300 mg tralokinumab every 2 weeks [Q2W] vs. placebo) and ECZTRA 3 (NCT03363854; 300 mg tralokinumab Q2W vs. placebo, both plus TCS as needed), and the ECZTRA 6 adolescent trial (NCT03526861; pooled 150 mg and 300 mg tralokinumab Q2W vs. placebo). Tralokinumab-treated patients received a loading dose. Proportion of patients achieving IGA 0/1 and EASI-75 at Week 16 according to patient-reported current or past atopic comorbidity are presented as observed regardless of rescue medication use; missing data were imputed as non-responders. 
 Results: In total 2,223 patients were included across four trials. Among patients in ECZTRA 1 and 2, 50.5% reported history of asthma, 38.5% food allergy, 53.8% hay fever, and 33.5% allergic conjunctivitis, while 19.8% reported no atopic comorbidities and 79.3% reported ≥1 atopic comorbidity. Proportions of patients in ECZTRA 3 and 6 reporting history of atopic comorbidities were largely similar, although more adolescent patients reported food allergy. In all subgroups at Week 16, higher proportions of patients receiving tralokinumab vs. placebo achieved EASI-75. In ECZTRA 1 and 2, response rates among patients in each subgroup were asthma: 35.3% vs. 12.8%, food allergy: 33.2% vs. 14.7%, hay fever: 36.8% vs. 16.5%, allergic conjunctivitis: 34.8% vs. 12.7%, none: 34.6% vs. 20.5%; and ≥1 atopic comorbidity: 35.5% vs. 15.2% (P<0.05 for all). A similar pattern of response was observed in ECZTRA 3 and 6, and for IGA 0/1 across trials. EASI-75 response rates for tralokinumab-treated patients were consistent across patients with different numbers of atopic comorbidities. Safety across subgroups was consistent with the safety profile of tralokinumab observed overall in adults and adolescents.
 Conclusions: 16 weeks of tralokinumab treatment improved AD signs and symptoms in adult and adolescent patients with and without atopic comorbidities, regardless of type or number of atopic comorbidities. The safety profile of tralokinumab was consistent between patients with and without atopic comorbidities.

The Occurrence of Atopy in Patients with Isolated Spontaneous Mast Cell (or Nonallergic) Angioedema.

Isolated mast cell angioedema (MC-AE) can be divided into allergic and nonallergic (spontaneous) forms. The former is often associated with food, Hymenoptera venoms or drug allergies. This study aimed to evaluate the relationship between the occurrence of atopic diseases and the risk of angioedema. A retrospective study analyzed 304 patients with confirmed MC-AE and 1066 controls. All were analyzed for allergic asthma (AA), atopic dermatitis (AD) and allergic rhinitis (AR) based on ICD-10 codes. In addition, total IgE and peripheral eosinophilia were calculated. The analyzed atopic diseases were more frequent in the group of patients diagnosed with MC-AE than in the controls: 78 (25.7%) vs. 173 (16.2%) for p < 0.01. Patients diagnosed with AD had a higher risk of MC-AE (hazard ratio (HR) = 1.48,) similar to those diagnosed with AR (HR = 1.51). However, in patients with two or three atopic comorbidities, the risk increased significantly to HR = 2.45 or HR = 4.1, respectively. There was a positive correlation between the serum total IgE concentration or eosinophilia and the risk of angioedema (p < 0.01). Patients with MC-AE had a more frequent occurrence of atopic diseases associated with inhalant allergies. This risk increased in patients with IgE-mediated polymorphic disease.

Does Comorbid Food Allergy Affect Response to Omalizumab in Patients with Asthma?

The intrinsic link between food allergy and asthma is well-established, and comorbidity can exacerbate both conditions. Omalizumab, an anti-immunoglobulin E (IgE) antibody, has the biological plausibility to manage both conditions, but only a few small studies have assessed omalizumab in patients with comorbid asthma and food allergy. We conducted a post hoc analysis of placebo-controlled, randomized clinical trials (IA05 in children and 008/009 in adolescents/adults) and real-world observational studies (EXCELS and PROSPERO). For each study, patients with asthma were stratified by whether they had physician-reported food allergy, as per baseline characteristics data. For patients with comorbid food allergy, there was evidence for increased atopy at baseline (numerically higher total IgE levels and atopic comorbidities). The collective body of evidence found that omalizumab consistently improved general and asthma-specific patient-centered outcomes (food allergy-specific outcomes were not available). For patients with asthma, omalizumab improved healthcare resource use (emergency room visits, hospitalizations, unscheduled doctor visits), quality of life (asthma-specific Asthma Quality of Life Questionnaire), productivity (missed work/school days and the Work Productivity and Activity Impairment: Asthma), and asthma outcomes (asthma exacerbations and Asthma Control Test score) regardless of comorbid food allergy. There was no loss of omalizumab efficacy even though patients with both asthma and food allergy appeared to be generally more atopic. Omalizumab may be a viable management option for patients with these comorbidities. NCT00079937; NCT01922037; NCT00252135.

Higher occurrence of ocular surface disease symptoms in patients with atopic dermatitis—Data in the FOREVER study

Aims/Purpose: Atopic Dermatitis (AD) is a common inflammatory skin disease that often begins in early childhood and may continue into adulthood. AD severity, and comorbid bronchial asthma and rhinitis have been associated with increased prevalence of Ocular Surface Diseases (OSD) in AD patients (1). OSD is common in the general population and symptoms from the ocular surface do not always lead to examination and diagnosis by healthcare professionals. The purpose of this study was to investigate the occurrence of self‐reported symptoms from the ocular surface in AD patients compared to the population without AD.Methods: A questionnaire study was conducted as a part of project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability) to examine the relationship between eye and overall health in Danish citizens. Symptoms related to the ocular surface included tearing, blurred vision, red, itching, burning, gritty, and dry eyes. Logistic regression models were used to investigate associations between AD and the occurrence of symptoms related to the ocular surface.Results: 36874 people had completed the FOREVER questionnaire. 797, 3305 and 32 772 participants answered that they have current AD, previously had AD, and never had AD, respectively. 69% (550/797) and 67% (2201/3305) in the group with current AD and previous AD experienced one or more ocular surface symptoms compared to 60% (19 517/32 772) in the non‐AD group. The odds ratio of AD and ocular surface symptoms was 1.27 [1.09–1.48] (p &lt; 0.01) and 1.17 [1.08–1.26] (p &lt; 0.001) for current and previous AD when adjusting for age, sex, smoking status, and atopic comorbidities; bronchial asthma and rhinitis.Conclusions: Our study found that participants with AD from the FOREVER cohort reported a higher occurrence of OSD symptoms compared to participants who have never suffered from AD. This suggest that AD patients are at higher risk of developing OSD symptoms.Reference1. Rønnstad ATM, Hansen PM, Halling AS, et al. Factors associated with ocular surface disease and severity in adults with atopic dermatitis: a nationwide survey. J Eur Acad Dermatol Venereol. 2022;36(4):592–601.

Omega-5-gliadin-specific immunoglobulin E-positive, but wheat-specific immunoglobulin E-negative wheat allergy dependent on augmentation factors—a frequent presentation

Aim: Most patients with wheat allergy dependent on augmentation factors (WALDA) show specific immunoglobulin E (sIgE) to ω5-gliadin. However, some WALDA patients may show negative results when testing for sIgE to total wheat extract. This is the first study to investigate potential clinical and serological differences in patients with ω5-gliadin-positive, challenge-confirmed WALDA dependent on their sensitization to total wheat extract. Methods: Clinical and serological characteristics of patients with challenge-confirmed, ω5-gliadin-positive WALDA were analyzed based on the absence or presence of sIgE to wheat (cut-off 0.35 kUA/L). Results: Thirty-six patients with challenge-confirmed WALDA were included (19 female; median age 50.5 years; median sIgE to ω5-gliadin 6.5 kUA/L). SIgE levels to grass pollen were related to the presence of any atopic comorbidity (P &lt; 0.001) and showed a correlation with sIgE to wheat (P = 0.003), but not to the gluten-related allergens [all not significant (ns)]. Thirty-nine percent of patients (n = 14) showed sIgE levels to wheat lower than 0.35 kUA/L; in 19.4% (n = 7) levels were even below the detection limit of 0.01 kUA/L. WALDA patients without sIgE to wheat showed lower levels of total immunoglobulin E (IgE) and sIgE to wheat gluten, gliadins, and ω5-gliadin (all P &lt; 0.001) as well as to grass pollen (P = 0.03). No significant differences in clinical characteristics like delay until diagnosis, the presence of an atopic condition, reaction severity, or threshold in the oral challenge test were observed. Conclusions: SIgE to wheat extract was associated not only with sensitization against gluten allergens but also reflected total IgE production and concomitant grass pollen allergy, making it an insensitive and unspecific biomarker for WALDA. There were no clinical divergences between WALDA patients without or with sIgE to wheat. SIgE to total wheat extract does not appear to be clinically relevant and remains negative in a significant proportion of WALDA patients.

Gender differences in adult atopic dermatitis and clinical implication: Results from a nationwide multicentre study.

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults. However, limited research has been conducted on gender differences in AD. This study aimed to assess gender differences in adult AD patients, focusing on demographic and clinical features, comorbidities and treatment approaches. In this multicentre, observational, cross-sectional study, we enrolled 686 adult patients with AD (357 males and 329 females). For each patient, we collected demographic data (age and sex), anthropometric measurements (weight, height, hip circumference, waist circumference and waist-to-hip ratio), clinical information (onset age, disease duration, severity, itching intensity, impact on quality of life) and noted comorbidities (metabolic, atopic and other). We recorded past and current topical and systemic treatments. We analysed all collected data using statistical techniques appropriate for both quantitative and qualitative variables. Multiple correspondence analysis (MCA) was employed to evaluate the relationships among all clinical characteristics of the patients. We found no differences in age at onset, disease duration, severity and quality of life impact between males and females. Males exhibited higher rates of hypertriglyceridaemia and hypertension. No significant gender differences were observed in atopic or other comorbidities. Treatment approaches were overlapping, except for greater methotrexate use in males. MCA revealed distinct patterns based on gender, disease severity, age of onset, treatment and quality of life. Adult males with AD had severe disease, extensive treatments and poorer quality of life, while adult females had milder disease, fewer treatments and moderate quality of life impact. Our study reveals that gender differences in adult AD patients are largely due to inherent population variations rather than disease-related disparities. However, it highlights potential undertreatment of females with moderate AD and quality of life impact, emphasizing the need for equitable AD treatment. JAK inhibitors may offer a solution for gender-based therapeutic parity.

Biologic drugs, a new therapeutic paradigm in moderate-severe atopic dermatitis

Atopic dermatitis (AD), also referred to eczema, is a common inflammatory skin disease that usually presents during infancy or childhood but affects patients of all ages. It is a pruritic, chronic/relapsing condition that may significantly impact the patients’ quality of life and can be associated with other atopic comorbidities including asthma and rhinoconjunctivitis. Inflammation in AD is mostly sustained by type 2 inflammation. Most patients are satisfactorily managed with a combination of emollients, avoidance of triggering factors, topical glucocorticoids, and/or topical calcineurin inhibitors. However, a proportion of patients with moderate or severe AD might require phototherapy or systemic immunosuppressants, which are limited in time due to possible safety concerns and progressive efficacy loss. In recent years, the availability of T helper 2 (Th2)-blocking agents dupilumab and tralokinumab has revolutionized the long-term treatment of moderate-to-severe AD. Here are discussed recent advances in the clinical development of biologic treatments for AD. The clinical implementation of these novel drugs has the potential not only to greatly improve the quality of life of patients with this chronic and disabling condition but also to clarify the biological processes underlying AD, in turn enabling further development of more effective, safer treatments. This research paper aims to provide an overview of biological therapies currently in use and under investigation in the setting of AD.